Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify...

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Autores principales:	M Kamran Ikram, Xueling Sim, Richard A Jensen, Mary Frances Cotch, Alex W Hewitt, M Arfan Ikram, Jie Jin Wang, Ronald Klein, Barbara E K Klein, Monique M B Breteler, Ning Cheung, Gerald Liew, Paul Mitchell, Andre G Uitterlinden, Fernando Rivadeneira, Albert Hofman, Paulus T V M de Jong, Cornelia M van Duijn, Linda Kao, Ching-Yu Cheng, Albert Vernon Smith, Nicole L Glazer, Thomas Lumley, Barbara McKnight, Bruce M Psaty, Fridbert Jonasson, Gudny Eiriksdottir, Thor Aspelund, Global BPgen Consortium, Tamara B Harris, Lenore J Launer, Kent D Taylor, Xiaohui Li, Sudha K Iyengar, Quansheng Xi, Theru A Sivakumaran, David A Mackey, Stuart Macgregor, Nicholas G Martin, Terri L Young, Josh C Bis, Kerri L Wiggins, Susan R Heckbert, Christopher J Hammond, Toby Andrew, Samantha Fahy, John Attia, Elizabeth G Holliday, Rodney J Scott, F M Amirul Islam, Jerome I Rotter, Annie K McAuley, Eric Boerwinkle, E Shyong Tai, Vilmundur Gudnason, David S Siscovick, Johannes R Vingerling, Tien Y Wong
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/4bf4067a29b347a382d33d4accfb1e43
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spelling	oai:doaj.org-article:4bf4067a29b347a382d33d4accfb1e432021-11-18T06:17:55ZFour novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.1553-73901553-740410.1371/journal.pgen.1001184https://doaj.org/article/4bf4067a29b347a382d33d4accfb1e432010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21060863/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.M Kamran IkramXueling SimRichard A JensenMary Frances CotchAlex W HewittM Arfan IkramJie Jin WangRonald KleinBarbara E K KleinMonique M B BretelerNing CheungGerald LiewPaul MitchellAndre G UitterlindenFernando RivadeneiraAlbert HofmanPaulus T V M de JongCornelia M van DuijnLinda KaoChing-Yu ChengAlbert Vernon SmithNicole L GlazerThomas LumleyBarbara McKnightBruce M PsatyFridbert JonassonGudny EiriksdottirThor AspelundGlobal BPgen ConsortiumTamara B HarrisLenore J LaunerKent D TaylorXiaohui LiSudha K IyengarQuansheng XiTheru A SivakumaranDavid A MackeyStuart MacgregorNicholas G MartinTerri L YoungJosh C BisKerri L WigginsSusan R HeckbertChristopher J HammondToby AndrewSamantha FahyJohn AttiaElizabeth G HollidayRodney J ScottF M Amirul IslamJerome I RotterAnnie K McAuleyEric BoerwinkleE Shyong TaiVilmundur GudnasonDavid S SiscovickJohannes R VingerlingTien Y WongPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 6, Iss 10, p e1001184 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 M Kamran Ikram Xueling Sim Richard A Jensen Mary Frances Cotch Alex W Hewitt M Arfan Ikram Jie Jin Wang Ronald Klein Barbara E K Klein Monique M B Breteler Ning Cheung Gerald Liew Paul Mitchell Andre G Uitterlinden Fernando Rivadeneira Albert Hofman Paulus T V M de Jong Cornelia M van Duijn Linda Kao Ching-Yu Cheng Albert Vernon Smith Nicole L Glazer Thomas Lumley Barbara McKnight Bruce M Psaty Fridbert Jonasson Gudny Eiriksdottir Thor Aspelund Global BPgen Consortium Tamara B Harris Lenore J Launer Kent D Taylor Xiaohui Li Sudha K Iyengar Quansheng Xi Theru A Sivakumaran David A Mackey Stuart Macgregor Nicholas G Martin Terri L Young Josh C Bis Kerri L Wiggins Susan R Heckbert Christopher J Hammond Toby Andrew Samantha Fahy John Attia Elizabeth G Holliday Rodney J Scott F M Amirul Islam Jerome I Rotter Annie K McAuley Eric Boerwinkle E Shyong Tai Vilmundur Gudnason David S Siscovick Johannes R Vingerling Tien Y Wong Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
description	There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
format	article
author	M Kamran Ikram Xueling Sim Richard A Jensen Mary Frances Cotch Alex W Hewitt M Arfan Ikram Jie Jin Wang Ronald Klein Barbara E K Klein Monique M B Breteler Ning Cheung Gerald Liew Paul Mitchell Andre G Uitterlinden Fernando Rivadeneira Albert Hofman Paulus T V M de Jong Cornelia M van Duijn Linda Kao Ching-Yu Cheng Albert Vernon Smith Nicole L Glazer Thomas Lumley Barbara McKnight Bruce M Psaty Fridbert Jonasson Gudny Eiriksdottir Thor Aspelund Global BPgen Consortium Tamara B Harris Lenore J Launer Kent D Taylor Xiaohui Li Sudha K Iyengar Quansheng Xi Theru A Sivakumaran David A Mackey Stuart Macgregor Nicholas G Martin Terri L Young Josh C Bis Kerri L Wiggins Susan R Heckbert Christopher J Hammond Toby Andrew Samantha Fahy John Attia Elizabeth G Holliday Rodney J Scott F M Amirul Islam Jerome I Rotter Annie K McAuley Eric Boerwinkle E Shyong Tai Vilmundur Gudnason David S Siscovick Johannes R Vingerling Tien Y Wong
author_facet	M Kamran Ikram Xueling Sim Richard A Jensen Mary Frances Cotch Alex W Hewitt M Arfan Ikram Jie Jin Wang Ronald Klein Barbara E K Klein Monique M B Breteler Ning Cheung Gerald Liew Paul Mitchell Andre G Uitterlinden Fernando Rivadeneira Albert Hofman Paulus T V M de Jong Cornelia M van Duijn Linda Kao Ching-Yu Cheng Albert Vernon Smith Nicole L Glazer Thomas Lumley Barbara McKnight Bruce M Psaty Fridbert Jonasson Gudny Eiriksdottir Thor Aspelund Global BPgen Consortium Tamara B Harris Lenore J Launer Kent D Taylor Xiaohui Li Sudha K Iyengar Quansheng Xi Theru A Sivakumaran David A Mackey Stuart Macgregor Nicholas G Martin Terri L Young Josh C Bis Kerri L Wiggins Susan R Heckbert Christopher J Hammond Toby Andrew Samantha Fahy John Attia Elizabeth G Holliday Rodney J Scott F M Amirul Islam Jerome I Rotter Annie K McAuley Eric Boerwinkle E Shyong Tai Vilmundur Gudnason David S Siscovick Johannes R Vingerling Tien Y Wong
author_sort	M Kamran Ikram
title	Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
title_short	Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
title_full	Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
title_fullStr	Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
title_full_unstemmed	Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
title_sort	four novel loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/4bf4067a29b347a382d33d4accfb1e43
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Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.

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